title: The IRAK homolog Pelle is the functional counterpart of IκB kinase in the Drosophila Toll pathway.
abstract: Toll receptors transduce signals that activate Rel-family transcription factors, such as NF-κB, by directing proteolytic degradation of inhibitor proteins. In mammals, the IκB Kinase (IKK) phosphorylates the inhibitor IκBα. A βTrCP protein binds to phosphorylated IκBα, triggering ubiquitination and proteasome mediated degradation. In Drosophila, Toll signaling directs Cactus degradation via a sequence motif that is highly similar to that in IκBα, but without involvement of IKK. Here we show that Pelle, the homolog of a mammalian regulator of IKK, acts as a Cactus kinase. We further find that the fly βTrCP protein Slimb is required in cultured cells to mediate Cactus degradation. These findings enable us for the first time to trace an uninterrupted pathway from the cell surface to the nucleus for Drosophila Toll signaling.
authors.affiliation: Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Daigneault
authors.forename: Liv
authors.initials: L
authors.lastname: Klemetsaune
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wasserman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C110233:slmb protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C079896:pll protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; C496563:IKKbeta protein, Drosophila